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P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years).We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults.Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality.In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

Background Candida bloodstream infections (BSI) became an important invasive disease in the late 20th century, in particular among immunocompromised patients. Although considerable progress has been made in the management of patients with invasive mycoses, Candida BSI are still widespread among hospitalised patients and are associated with relatively high mortality. Objectives We conducted a retrospective study to evaluate patient characteristics, incidence, species distribution and antifungal susceptibility of BSI isolates of Candida spp. as well as outcomes of Candida BSI from 2001 to 2012, before the widespread use of echinocandins. This is the first epidemiological study of Candida BSI in Slovenia so far. Methods All documented candidaemia cases from 2001 to 2012 in two major hospitals-University Medical Centre and Institute of Oncology in Ljubljana, Slovenia-were taken into consideration. Candida BSI were identified in 422 patients (250 male, 172 female). Laboratory and clinical data of these patients were retrospectively analysed. Mann-Whitney U test was used to compare continuous variables and Fisher's exact test or chi-squared test for categorical variables. Results and conclusions The average incidence of Candida BSI was 0.524/10.000 patient-days (0,317/1000 admissions); 16/422 were younger than 1 year and 251/422 patients were over 60 years old. The most commonly isolated species were Candida albicans and Candida glabrata, followed by Candida parapsilosis. Majority of the patients had a single episode of Candida BSI, multiple episodes of Candida BSI occurred in 18/434 patients (4.1%); in 25/434 patients (5.8%) mixed Candida BSI were observed. Crude 30-day case-fatality rate was 55.4%.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

Bacteroides fragilis can be classified into division I (cfiA negative) and division II (cfiA positive) isolates. Division II isolates have a silent chromosomal carbapenemase gene (cfiA) that can become overexpressed by an insertion of a mobile genetic element and thus develop a phenotypic resistance to carbapenems. Aims of our study were (i) to determine the prevalence of B. fragilis division II (cfiA positive) isolates among blood stream and non-blood stream isolates from two major Slovenian tertiary-care hospitals and (ii) to assess its influence on phenotypic resistance to imipenem. Consecutive non-duplicate B. fragilis isolates from blood stream and non-blood stream specimens were included in the analysis from 2015 to 2017 period. Data from laboratory information system were matched with mass spectra obtained with Microflex LT instrument and MALDI Biotyper 3.1 software (Bruker Daltonik, Bremen, Germany). All mass spectra were reanalyzed using Bruker taxonomy library. Spectra with a log(score) > 2.0 were further analyzed with cfiA library that separates B. fragilis division I and II isolates based on a log(score) value difference of >0.3. Minimal inhibitory concentrations (MICs) for imipenem were determined with Etest (bioMerieux, Marcy l’Etoile, France), using supplemented Brucella agar and EUCAST breakpoints (S ≤ 2 mg/L, R > 8 mg/L). Altogether 623 consecutive B. fragilis isolates were included in the analysis; 47 (7.5%) were isolated from blood stream and 576 (92.5%) from non-blood stream specimens. Among all study isolates, 51 (8.2%) proved to belong to division II (cfiA positive). The proportions of division II isolates among blood stream and non-blood stream isolates were 14.9% and 7.6%, respectively (p = 0.081, ns). In total, 1.3% (n = 8) were non-susceptible to imipenem (MIC >2 mg/L); 4.3% (n = 2) among blood stream and 1% (n = 6) among non-blood stream isolates. All imipenem resistant isolates belonged to division II. Modal MICs (MIC range) were 0.064 mg/L (0.016 mg/L-2 mg/L) and 0.125 mg/L (0.064 mg/L-≥32 mg/L) for division I and II isolates, respectively.

[Background] Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality., [Methods] This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009–15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy., [Results] Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64–1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens., [Conclusions] In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.

This study was presented as poster presentation at the European Society of Clinical Microbiology and Infectious Diseases annual conference, Madrid, Spain, 21–24 April 2018., [Background] The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although β-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. [Methods] A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with β-lactam monotherapy during 2009–2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. [Results] Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52–2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67–2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). [Conclusions] No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection., This study was conducted with no external funding. In Sweden only, the research was funded by grants from the Stockholm County Council and Emil and Wera Cornell Foundation.

This study aimed to evaluate risk factors for 30-day mortality among hospitalised patients with Pseudomonas aeruginosa bacteraemia, a highly fatal condition. A retrospective study was conducted between 1 January 2009 and 31 October 2015 in 25 centres (9 countries) including 2396 patients. Univariable and multivariable analyses of risk factors were conducted for the entire cohort and for patients surviving >= 48 h. A propensity score for predictors of appropriate empirical therapy was introduced into the analysis. Of the 2396 patients, 636 (26.5%) died within 30 days. Significant predictors (odds ratio and 95% confidence interval) of mortality in the multivariable analysis included patient-related factors: age (1.02, 1.01-1.03); female sex (1.34, 1.03-1.77); bedridden functional capacity (1.99, 1.24-3.21); recent hospitalisation (1.43, 1.07-1.92); concomitant corticosteroids (1.33, 1.02-1.73); and Charlson comorbidity index (1.05, 1.01-1.93). Infection-related factors were multidrug-resistant Pseudomonas (1.52, 1.15-2.1), nonurinary source (2.44, 1.54-3.85) and Sequential Organ Failure Assessment (SOFA) score (1.27, 1.18-1.36). Inappropriate empirical therapy was not associated with increased mortality (0.81, 0.49-1.33). Among 2135 patients surviving >= 48 h, hospital-acquired infection (1.59, 1.21-2.09), baseline endotracheal tube (1.63, 1.13-2.36) and ICU admission (1.53, 1.02-2.28) were additional risk factors. Risk factors for mortality among patients with P. aeruginosa were mostly irreversible. Early appropriate empirical therapy was not associated with reduced mortality. Further research should be conducted to explore subgroups that may not benefit from broad-spectrum antipseudomonal empirical therapy. Efforts should focus on prevention of infection, mainly hospital-acquired infection and multidrug-resistant pseudomonal infection. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

The aim of our study was to determined antimicrobial susceptibility profiles of 2673 clinically significant anaerobic bacteria belonging to the major genera, isolated in 2015 in a large tertiary-care hospital in Slovenia. The species identification was performed by MALDI-TOF mass spectrometry. Antimicrobial susceptibility was determined immediately at the isolation of the strains against: penicillin, co-amoxiclav, imipenem, clindamycin and metronidazole, using gradient diffusion methodology and EUCAST breakpoints. The most frequent anaerobes were Bacteroides fragilis group with 31% (n = 817), Gram positive anaerobic cocci (GPACs) with 22% (n = 589), Prevotella with 14% (n = 313) and Propionibacterium with 8% (n = 225). Metronidazole has retained full activity (100%) against all groups of anaerobic bacteria intrinsically susceptible to it. Co-amoxiclav and imipenem were active against most tested anaerobes with zero or low resistance rates. However, observed resistance to co-amoxiclav (8%) and imipenem (1%) is worrying especially among B. fragilis group isolates. High overall resistance (23%) to clindamycin was detected in our study and was highest among the genera Prevotella, Bacteroides, Parabacteroides, GPACs and Clostridium. Routine testing of antimicrobial susceptibility of clinically relevant anaerobic bacteria is feasible and provides good surveillance data.

In patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E), the preference for carbapenems (CRBs) over non-CRB antibiotics for empirical therapy of sepsis is questionable from an ecologic perspective. Moreover, how well colonisation predicts an ESBL-E aetiology of infection has been poorly investigated. The purpose of this retrospective observational study was to determine the positive predictive value (PPV) of ESBL-E faecal colonisation for ESBL-E sepsis aetiology and the impact of empirical therapy on treatment outcome. The study included 653 ESBL-E carriers with community-onset sepsis hospitalised at a single medical centre during a 5-year period. The PPV of ESBL-E colonisation for ESBL-E sepsis aetiology was significantly higher (62.6%) when sepsis originated from a urinary tract infection (UTI) than from a respiratory tract infection (24.5%), other known origins (27.1%) or an unidentified origin (21.4%). Among the 653 patients, 177 (27.1%) received CRBs empirically and 476 received non-CRBs, predominantly β-lactam/β-lactamase inhibitor combinations. Although univariate analysis suggested a higher 30-day mortality in the non-CRB versus CRB group (26.7% vs. 19.2%; OR = 1.53; P = 0.049), the estimated association was much smaller and was not significant (OR = 1.11, 95% CI 0.66-1.87; P = 0.68) in the multiple regression analysis adjusted for age, sex, Charlson comorbidity index, and severity, origin or aetiology of sepsis. The subgroup of 240 patients with unidentified sepsis aetiology also did not benefit from empirical CRB treatment. In non-critically ill ESBL-E carriers with community-onset sepsis, CRB-sparing empirical therapy seems appropriate, particularly if sepsis originates from a site other than a UTI.

Acinetobacter baumannii primarily causes colonization, yet it can be an opportunistic pathogen associated with hospital-acquired infections. Many countries report rapid spread of carbapenem-resistant Acinetobacter baumannii (CRAb) which limits treatment options, with colistin frequently being the last line treatment option. The aim of our study was to evaluate a recently developed rapid method, namely the Rapid ResaPolymyxin test, for detection of colistin resistance (ColR) in Acinetobacter baumannii. This test was used for rapid screening of colistin resistance in a clinical setting where there is endemicity of CRAb isolates. A total of 82 A. baumannii clinical isolates were included in the evaluation. The majority of them were resistant to carbapenems (75/82, 91.5%). A total of 37 isolates (45.1%) were resistant to colistin, all being resistant to carbapenems. None of the ColR isolates carried the plasmid- mediated mcr-1 to -5 genes. The Rapid ResaPolymyxin NP test reached a 95.1% categorical agreement with results of reference broth microdilution method, with 93.3% sensitivity and specificity, and positive and negative predictive values being respectively at 92.3% and 97.7%. The Rapid ResaPolymyxin NP test performed well on our collection of clinical and surveillance CRAb isolates from the Central Slovenia region. The test is inexpensive and easy to integrate into laboratory workflow. The main value of the test is rapid categorization of susceptibility and resistance which has important implications with respect to the treatment strategy as well as the infection control measures.

Decreasing cephalosporin use was described as an effective intervention in decreasing the incidence of infections caused by Klebsiella pneumoniae harbouring extended-spectrum beta-lactamase (ESBLKP). Due to sustained increased levels of infections caused by ESBLKP, a multifaceted antibiotic stewardship intervention aimed to decrease cephalosporin use was carried out at a large medical unit of a teaching hospital. All cephalosporins except the first-generation were restricted and could only be prescribed after authorization by an infectious disease physician. The use of cephalosporins decreased significantly after intervention. The effect was most prominent for the third-generation cephalosporins (7.9-1.5 DDD/100 OBD). There was an increase in the consumption of piperacillin/tazobactam, carbapenems and fluoroquinolones. In contrast to our expectations the ESBLKP incidence increased, but the changes were not statistically significant. The intervention was successful in controlling the prescribing of cephalosporins, but had no impact on incidence of ESBLKP infections.

Background: Streptococcus agalactiae (group B streptococcus, GBS) is the leading cause of invasive neonatal infections in the developed world. We present epidemiological and clinical characteristics of invasive GBS disease among Slovenian neonates between 2003 and 2013.Methods: A retrospective cohort study was performed. Children aged 0–90 days with invasive GBS disease, born in Slovenia and hospitalized in the University Medical Centre Ljubljana were included. Cases were identified concurrently from (i) hospital and (ii) microbiological databases. Medical records from mothers and children were reviewed and relevant data extracted. The incidence rate was calculated based on the national vital statistics data and expressed per 1000 live births.Results: Altogether, 144 children were included in the analysis, 72.9 % (n = 105) based on hospital database and 27.1 % (n = 39) based on microbiological database. Among them, 47.9 % (n = 69) were girls and 52.1 % (n = 75) boys. Among the cases with available data, 54.5 % (n = 73) were born at term and 45.5 % (n = 61) were preterm. Early-onset disease (0–6 days) was present in 74.3 % (n = 107) of patients; 95.3 % (n = 102) of them became ill during the first 3 days of life. Late-onset disease (7–90 days) was present in 25.7 % (n = 37) of patients. Outcome data was available for 134 children. Neonatal mortality rate was 4.5 % (n = 6). Periventricular leukomalacia (PVL) or intraventricular haemorrhages Grade III/IV (IVH 3/4) were detected in 17.9 % (n = 24). Severe outcomes (death or PVL or IVH 3/4) were detected in 22.4 % (n = 30) children. Cumulative incidence rate was 0.72/1000 live births; 0.53/1000 for early-onset and 0.18/1000 for late-onset disease. Risk factors for early-onset disease were present in 47.9 % (n = 68) mothers in labour. Intrapartum antibiotic prophylaxis was delivered to 16.9 % (n = 24) of mothers.Conclusions: High incidence of invasive neonatal GBS disease was detected in Slovenia. Although low mortality was observed, brain pathology concordant with long-term adverse outcome was confirmed in a high proportion of patients. The application of intrapartum antibiotic prophylaxis in cases of known risk factors was suboptimal, especially among preterm deliveries. Approximately half of the patients were born to mothers without any risk factors. A comprehensive national strategy for the prevention of invasive GBS disease is warranted in Slovenia.

Rapid detection and identification of anaerobic bacteria from blood is important to adjust antimicrobial therapy by including antibiotics with activity against anaerobic bacteria. Limited data is available about direct identification of anaerobes from positive blood culture bottles using MALDI-TOF mass spectrometry (MS). In this study, we evaluated the performance of two sample preparation protocols for direct identification of anaerobes from positive blood culture bottles, the MALDI Sepsityper kit (Sepsityper) and the in-house saponin (saponin) method. Additionally, we compared two blood culture bottle types designed to support the growth of anaerobic bacteria, the BacT/ALERT-FN Plus (FN Plus) and the BACTEC-Lytic (Lytic), and their influence on direct identification. A selection of 30 anaerobe strains belonging to 22 different anaerobic species (11 reference strains and 19 clinical isolates) were inoculated to 2 blood culture bottle types in duplicate. In total, 120 bottles were inoculated and 99.2% (n = 119) signalled growth within 5 days of incubation. The Sepsityper method correctly identified 56.3% (n = 67) of anaerobes, while the saponin method correctly identified 84.9% (n = 101) of anaerobes with at least log(score) ≥1.6 (low confidence correct identification), (p

We studied the performance characteristics of two blood culture (BC) bottles/systems, (i) BacT/ALERT-FN Plus/3D (bioMérieux, Marcy l'Étoile, France) and (ii) BACTEC-Lytic/9000 (Becton Dickinson, Sparks, USA) for detection of growth and time-to-positivity (TTP) against a balanced and diverse collection of anaerobic bacterial strains (n = 48) that included reference strains (n = 19) and clinical isolates (n = 29) of 32 species (15 Gram-negative and 17 Gram-positive). Standard suspension of bacteria was inoculated to each bottle in duplicates and incubated in the corresponding system. Overall, 62.5% (n = 30) of strains were detected by both BC bottle types. Comparing the two, 70.8% (n = 34) and 79.2% (n = 38) of strains were detected by BacT/ALERT-FN Plus and BACTEC-Lytic bottles, respectively (p = 0.38). Among Gram-negative anaerobes (n = 25) the detection rate was 76.0% (n = 19) vs. 92.0% (n = 23) (p = 0.22), respectively. Among Gram-positive anaerobes (n = 23) the detection rate was 65.2% (n = 15) in both bottles (p = 1). The average TTP per bottle was calculated only for the strains detected by both systems (n = 30) and was 40.85 h and 28.08 h for BacT/ALERT-FN Plus and BACTEC-Lytic, respectively (p 0.001). The mean difference was 12.76 h (95% CI: 6.21-19-31 h). Six anaerobic strains were not detected by any system, including Gram-negative Porphyromonas gingivalis, and five Gram-positive strains: Finegoldia magna, Peptostreptococcus anaerobius, Propionibacterium acnes, Clostridium novyi and Clostridium clostridioforme. Furthermore, Eggerthella lenta and Prevotella bivia were detected only by BacT/ALERT-FN Plus, while Prevotella disiens and Prevotella intermedia were detected only by BACTEC-Lytic bottles. There were no major differences in detection rate among clinical and reference strains. Anaerobic bacteria represent a minority of BC isolates, however, far from ideal detection rate was observed in this study for both tested bottle/system combinations. Nevertheless, in those cases where both gave positive signal, BACTEC-Lytic was superior to BacT/ALERT FN Plus with 12.76 h shorter mean TTP. Improvements of media in blood culture bottles available for detection of anaerobes are warranted.

Background Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .

We report our 1-year experience with modified GeneOhm™ MRSA assay (formerly IDI-MRSA) for pooled surveillance specimens in low methicillin-resistant Staphylococcus aureus (MRSA) prevalence clinical setting. We have successfully modified the GeneOhm™ MRSA assay protocol during the specimen preparation step by adding an extra washing step followed by pooling of up to 3 samples per patient (nose, skin, with or without throat) at the lysis step. The sensitivity of the modified assay compared with conventional cultivation was 94.3%, specificity 99.2%, negative predictive value 99.2%, and positive predictive value 94.3%. The modified test is reliable and performed well compared with conventional culture methods in our clinical setting with low-level prevalence of MRSA colonization. Our findings support the use of pooling of the patients samples as a cost-effective way of screening for MRSA colonization.

The implementation of routine whole-genome sequencing (WGS) promises to transform our ability to monitor the emergence and spread of bacterial pathogens. Here we combined WGS data from 308 invasive Staphylococcus aureus isolates corresponding to a pan-European population snapshot, with epidemiological and resistance data. Geospatial visualization of the data is made possible by a generic software tool designed for public health purposes that is available at the project URL (http:// www.microreact.org/project/EkUvg9uY?tt=rc). Our analysis demonstrates that high-risk clones can be identified on the basis of population level properties such as clonal relatedness, abundance, and spatial structuring and by inferring virulence and resistance properties on the basis of gene content. We also show that in silico predictions of antibiotic resistance profiles are at least as reliable as phenotypic testing. We argue that this work provides a comprehensive road map illustrating the three vital components for future molecular epidemiological surveillance: (i) large-scale structured surveys, (ii) WGS, and (iii) communityoriented database infrastructure and analysis tools. IMPORTANCE The spread of antibiotic-resistant bacteria is a public health emergency of global concern, threatening medical intervention at every level of health care delivery. Several recent studies have demonstrated the promise of routine wholegenome sequencing (WGS) of bacterial pathogens for epidemiological surveillance, outbreak detection, and infection control. However, as this technology becomes more widely adopted, the key challenges of generating representative national and international data sets and the development of bioinformatic tools to manage and interpret the data become increasingly pertinent. This study provides a road map for the integration of WGS data into routine pathogen surveillance. We emphasize the importance of large-scale routine surveys to provide the population context for more targeted or localized investigation and the development of open-access bioinformatic tools to provide the means to combine and compare independently generated data with publicly available data sets., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes.177 methicillin-resistant S. aureus (MRSA) isolates from infective endocarditis (IE), skin and soft tissue infection (SSTI), and hospital-acquired/ventilator-associated pneumonia (HAP) were matched by geographic origin, then genotyped using spa-typing. In vitro PSM production was measured by high performance liquid chromatography/mass spectrometry. Statistical analysis was performed using Chi-squared or Kruskal-Wallis tests as appropriate.Spa type 1 was significantly more common in SSTI isolates (62.7% SSTI; 1.7% IE; 16.9% HAP; p 0.0001) while HAP and IE isolates were more commonly spa type 2 (0% SSTI; 37.3% IE; 40.7% HAP; p 0.0001). USA300 isolates produced the highest levels of PSMs in vitro. SSTI isolates produced significantly higher quantities of PSMα1-4, PSMβ1, and δ-toxin than other isolates (p 0.001). These findings persisted when USA300 isolates were excluded from analysis.Increased in vitro production of PSMs is associated with an SSTI clinical source. This significant association persisted after exclusion of USA300 genotype isolates from analysis, suggesting that PSMs play a particularly important role in the pathogenesis of SSTI as compared to other infection types.

International audience; Background - The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods - Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results - EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions - In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Summary To study the epidemiology - especially the impact of contaminated stopcocks - on central venous catheter (CVC) infection and catheter-related sepsis (CRS), semi-quantitative (SQ) and quantitative (Q) culture methods and typing of coagulase-negative staphylococci (CNS) were employed in 49 neonates with clinical signs of sepsis while receiving parenteral nutrition in the paediatric intensive care unit. The patients were divided into two groups according to stopcock contamination: group A consisted of 18 patients (36%) with contaminated stopcocks and group B consisted of 31 patients (64%) with sterile stopcocks. Five specimens were obtained from each patient, in addition to that from the stopcock: a swab taken from the skin surrounding the catheter puncture site; the CVC tip; the intradermal segment (IDC); and samples of parenteral fluid and blood. A total of 294 specimens (392 sites) was cultured and micro-organisms were identified. All CNS isolated were typed by biotyping, antibiogram, plasmid analysis and pulsed-field gel electrophoresis (PFGE), and the discriminatory power of the typing methods was compared. The CVC tips were infected in 25 patients (51%); 15 (83%) in group A and 10 (32%) in group B. Sepsis was detected in 24 neonates (49%), 13 in group A and 11 in group B. This was catheter-related in 15 patients (63%), 12 in group A and 3 in group B. CNS were recovered from 13 (52%) of 25 infected CVCs, nine in group A and four in group B. Sixty-five CNS isolates were recovered from these patients and belonged to 14 biotypes, 22 antibiograms, 22 plasmid profiles and 26 PFGE types. Typing showed that in six of nine patients in group A, CNS of the same type were recovered from the catheter tip and the stopcock, in one patient the catheter tip and skin isolates were the same and in two others the catheter tip isolates were different from stopcock and skin isolates. In all four patients in group B, different CNS types were recovered from CVC tips and skin. Bacteraemia was caused by CNS in 14 patients (58%), six in group A and eight in group B. Typing confirmed that nine cases (six in group A and three in group B) were catheter-related but five were not. SQ and Q culture methods and typing, especially by PFGE, allowed the study to determine that bacteria from contaminated stopcocks were frequently the source of CVC infection and CRS.

To the Editor: Patients with cancer often consume probiotics as part of their diet, although therapeutic use of probiotics is not recommended because of their potential invasiveness. In a recent review, 5 cases of probiotic treatment–related bacteremia were identified in oncology patients, although no cases of invasive Bifidobacterium spp. infection were included (1). We describe a case of B. breve sepsis in a child with Philadelphia chromosome–positive acute B-cell lymphoblastic leukemia. The patient was a previously healthy 2-year-old boy who had no history of immunodeficiency and whose leukocyte counts had been within reference ranges during check-up visits before his diagnosis. After leukemia was diagnosed, chemotherapy was started (prednisone, vincristine, doxorubicin, and L-asparaginase). During the second week of treatment, the boy experienced abdominal discomfort and constipation. Two weeks later, his condition worsened; he refused food, his abdomen was distended, and he had colicky pain. Thickened intestinal wall and fecal masses were seen ultrasonographically. Twelve hours later he became hypotensive. Laboratory test results showed severe neutropenia and increased inflammatory markers (Figure). Two aerobic and anaerobic blood culture samples were collected from a central venous line (implantable venous access system) in a 30-minute span, and treatment with piperacillin/tazobactam, vancomycin, and gentamicin was empirically initiated according to local recommendations for pediatric febrile neutropenia with shock. Both anaerobic blood cultures were positive. Gram-positive, irregular rods with bifid and branching forms without spores grew anaerobically on blood agar with hemin and vitamin K after 48 hours of incubation and were identified as B. breve by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (Bruker Daltonics, Billerica, MA, USA). The bacteria were susceptible to penicillin (MIC 0.250 μg/mL), ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam (MIC 0.125 μg/mL), imipenem, and clindamycin but not metronidazole. Gentamicin and vancomycin were discontinued, and piperacillin/tazobactam was replaced by penicillin (Figure). The patient stayed afebrile, and his neutropenia resolved. A blood culture taken on the eighth day of antimicrobial drug treatment was negative, and the central venous line was not replaced at that time. Bowel movement normalized and was maintained. We reviewed the ingredients of the food that the child received and documented the presence of Lactobacillus spp. and B. longum but not B. breve. Figure Schematic presentation of leukocyte count, C-reactive protein, and procalcitonin serum levels in clinical course of Bifidobacterium breve sepsis. Arrows indicate the name and duration of each antimicrobial drug treatment. Some probiotics are part of the normal intestinal microbiota and rarely cause invasive infections (2). Although Bifidobacterium spp. is infrequently associated with infections (

5-Benzylidenethiazolidin-4-ones and 5-benzylidenepyrimidine-4,6-diones (compounds 1–9), carrying 2,3,4-trifluoro or 3,4,5-trimethoxy groups on the benzylidene moiety, and rhodanine derivatives 10 and 11 were synthesized and assayed in vitro for their antimicrobial activity against four standard bacterial strains (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). Compounds 1–3 and 9 that were active against S. aureus, were also tested against methicillin-resistant S. aureus (MRSA) ATCC 43300, Streptococcus pneumoniae ATCC 49619 and Streptococcus pyogenes ATCC 19615. (Z)-5-(2,3,4-Trifluorobenzylidene)rhodanine (1) inhibited the growth of S. aureus at 0.5 μg/mL and MRSA at 32 μg/mL. Stronger antimicrobial activity against S. aureus was observed for compounds bearing the rhodanine ring than those containing other heterocyclic moieties. Neither of the compounds 1–11 inhibited the growth of Gram-negative bacteria E. coli or P. aeruginosa.

Background: Antibacterial activity of three members of a benzoxazine series of histidine kinase inhibitors (4a, 4b and 6) was studied on standard strains, and with 4b also on clinical isolates of enterococci. Methods: Susceptibility to each compound was tested using a broth macrodilution method with a range of dilutions from 0.016 to 128 μg/ml on four standard strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212) and in the case of 4b also on 52 clinical isolates of enterococci (7 vancomycin-susceptible E. faecalis, 15 vancomycin-susceptible Enterococcus faecium and 30 vancomycin-resistant E. faecium), and on two additional standard strains (S. aureus ATCC 43300 and E. faecalis ATCC 51299). Results: Neither of the compounds inhibited the growth of E. coli ATCC 25922 or P. aeruginosa ATCC 27853. Compound 4b inhibited the growth of S. aureus ATCC 29213 at 8 μg/ml, S. aureus ATCC 43300 at 32 μg/ml, E. faecalis ATCC 29212, and E. faecalis ATCC 51299 at 16 μg/ml, while 4a and 6 did so at higher concentrations. For clinical isolates of enterococci, the minimal inhibitory concentrations of 4b were in the range of 0.5–16 μg/ml. Conclusions: Compound 4b promises to be a potentially useful antimicrobial agent for vancomycin-susceptible and -resistant enterococci.

Endocarditis due to Abiotrophia sp. is rare and often associated with negative blood cultures. The rates of treatment failure, infection relapse and mortality are higher than in endocarditis caused by other viridans streptococci.A retrospective review of A. defectiva endocarditis in a patient with prosthetic aortic valve and in a patient with Marfan syndrome was performed.A. defectiva, susceptible to penicillin (MIC 0.064 mg/l and 0.016 mg/l, respectively) was isolated from blood cultures of both patients. Treatment with penicillin and gentamicin was started in both patients. Since the first patient developed a macular rash and leukopenia, penicillin was substituted with ceftriaxone. Both patients responded well to antibiotic treatment, did not need prosthetic valve insertion or reinsertion, and were without any sequelae at one year follow up.Standard treatment of bacterial endocarditis with penicillin and gentamicin was effective in both patients. In contrast to previous reports, the present patients had a favorable outcome on completion of treatment and at one-year follow up.

Nosocomial infections at a department of neurosurgery were followed prospectively. In 1999, a high incidence of nosocomial lower respiratory tract infections (NLRTI) was observed in patients after intracranial artery aneurysm surgery (ICAAS). From February to December 2000, a short course of ciprofloxacin and co-trimoxazole was given prophylactically to all patients with ICAAS. The incidence of nosocomial infections in patients after ICAAS fell from 78.4 to 30.9% (P

Six consecutive methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained in a 2-month period from tracheal aspirates of six intensive care unit (ICU) patients with nosocomial pneumonia and two MRSA isolates from nasal carriers among staff were typed to determine whether one or more strains were involved and whether nasal carriage was the source of the outbreak. Pulsed-field gel electrophoresis (PFGE) of chromosomal DNA was used to type MRSA isolates. The typing showed that the outbreak was caused by a single epidemic MRSA clone. The MRSA strain isolated from the staff was unrelated to the outbreak strain and was therefore not the source of the outbreak in this study. The source was apparently the index patient followed by transfer of MRSA to other patients on medical equipment or on the hands of staff who did not adhere strictly to infection control measures.

Leptotrichia species typically colonize the oral cavity and genitourinary tract. We report the first two cases of endocarditis secondary to L. goodfellowii sp. nov. Both cases were identified using 16S rRNA gene sequencing. Review of the English literature revealed only two other cases of Leptotrichia sp. endocarditis.